tbuckley/cabot-search huggingface dataset:
A phase I/II study of intrathecal trastuzumab in human epidermal growth factor receptor 2-positive (HER2-positive) cancer with leptomeningeal metastases: Safety, efficacy, and cerebrospinal fluid pharmacokinetics
Authors: Priya U Kumthekar, Michael J Avram, Andrew B Lassman, Nancy U Lin, Eudocia Lee, Sean A Grimm, Margaret Schwartz, Kirsten L Bell Burdett, Rimas V Lukas, Karan Dixit, Isabella Perron, Hui Zhang, William J Gradishar, Elena I Pentsova, Suriya Jeyapalan, Morris D Groves, Michelle Melisko, Jeffrey J Raizer
Journal: Neuro-Oncology (2022)

Abstract Background Patients with human epidermal growth factor receptor 2-positive (HER2-positive) cancers have a high incidence of central nervous system (CNS) spread, but unfortunately systemic trastuzumab which targets the HER2 receptor has little CNS penetration. The purpose of this study was to determine the maximum-tolerated dose of intrathecal trastuzumab and its efficacy in patients with HER2-positive leptomeningeal disease (LMD). Methods This multicenter study enrolled 34 LMD patients in a combined phase I/II study in treating patients with intrathecal trastuzumab. Any HER2-positive histology was allowed in the phase I; the phase II was limited to HER2-positive breast cancer. Results Intrathecal trastuzumab was well-tolerated, with one dose limiting toxicity of grade 4 (arachnoiditis) occurring at the 80 mg twice weekly dose. The recommended phase II dose was 80 mg intrathecally twice weekly. Twenty-six patients at dose level 80 mg were included in evaluation for efficacy: partial response was seen in 5 (19.2%) patients, stable disease was observed in 13 (50.0%), and 8 (30.8%) of the patients had progressive disease. Median overall survival (OS) for phase II dose treated patients was 8.3 months (95% CI 5.2–19.6). The phase II HER2-positive breast cancer patients median OS was 10.5 months (95% CI 5.2–20.9). Pharmacokinetic (PK) studies were limited in the setting of concurrent systemic trastuzumab administration, however, did show stable cerebrospinal fluid (CSF) concentrations with repeated dosing suggest that trastuzumab does not accumulate in the CSF in toxic concentrations. Conclusion This study suggests promise for potentially improved outcomes of HER-positive LMD patients when treated with intrathecal trastuzumab while remaining safe and well-tolerated for patients.
Ozanimod: A Review in Ulcerative Colitis
Authors: Julia Paik
Journal: Drugs (2022)

Ozanimod (Zeposia®) is the first sphingosine-1-phosphate receptor (S1PR) modulator to be approved for the treatment of adults with moderately to severely active ulcerative colitis in the USA, and in adults with moderately to severely active ulcerative colitis who have had an inadequate or lost response to, or were intolerant of, either conventional therapy or a biologic in the EU. An oral agent, ozanimod is administered once daily as induction and maintenance therapy. In the randomized, double-blind, multinational phase 2 Touchstone and phase 3 True North clinical trials, ozanimod was effective in inducing clinical remission and maintaining remission relative to placebo in adults with moderately to severely active ulcerative colitis. Ozanimod was generally well tolerated in these studies, with manageable or transient adverse events (AEs). Current data from the Touchstone and True North open-label extensions are consistent with the primary studies with respect to therapeutic efficacy and tolerability, with no new safety signals observed. Although further data will be beneficial, ozanimod expands the treatment options for adults with moderately to severely active ulcerative colitis. Ulcerative colitis is a chronic inflammatory bowel disease involving a dysregulated immune response in the intestinal mucosa. Conventional therapy options for moderate to severe ulcerative colitis are initially effective, but associated with increased risk of adverse events, resistance to treatment, or loss of response over time. Consequently, small molecule drugs have become of interest as alternative treatment options. Ozanimod (Zeposia®) is an oral drug that targets and modulates the activity of sphingosine-1-phosphate receptors to reduce the movement of lymphocytes from the lymph nodes to sites of inflammation. Compared with placebo, ozanimod significantly improved rates of clinical remission and was generally well tolerated in adults with moderately to severely active ulcerative colitis. Findings from open-label extension studies suggest that ozanimod remains efficacious and generally well tolerated with long-term use. Although further data will be beneficial, ozanimod expands the treatment options for adults with moderately to severely active ulcerative colitis.
Toward the next generation of vascularized human neural organoids
Authors: Minghui Li, Lixiong Gao, Ling Zhao, Ting Zou, Haiwei Xu
Journal: Medicinal Research Reviews (2022)

Thanks to progress in the development of three-dimensional (3D) culture technologies, human central nervous system (CNS) development and diseases have been gradually deciphered by using organoids derived from human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs). Selforganized neural organoids (NOs) have been used to mimic morphogenesis and functions of specific organs in vitro. Many NOs have been reproduced in vitro, such as those mimicking the human brain, retina, and spinal cord. However, NOs fail to capitulate to the maturation and complexity of in vivo neural tissues. The persistent issues with current NO cultivation protocols are inadequate oxygen supply and nutrient diffusion due to the absence of vascular networks. In vivo, the developing CNS is interpenetrated by vasculature that not only supplies oxygen and nutrients but also provides a structural template for neuronal growth. To address these deficiencies, recent studies have begun to couple NO culture with bioengineering techniques and methodologies, including genetic engineering, coculture, multidifferentiation, microfluidics and 3D bioprinting, and transplantation, which might promote NO maturation and create more functional NOs. These cutting-edge methods could generate an ever more reliable NO model in vitro for deciphering the codes of human CNS development, disease progression, and translational application. In this review, we will summarize recent technological advances in culture strategies to generate vascularized NOs (vNOs), with a special focus on cerebral- and retinal-organoid models.
Facilitators and Barriers to Implementation of Lung Cancer Screening: A Framework-Driven Systematic Review
Authors: Ami E Sedani, Olivia C Davis, Shari C Clifton, Janis E Campbell, Ann F Chou
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract Background The purpose of this study is to undertake a comprehensive systematic review to describe multilevel factors (barriers and facilitators) that may influence the implementation of low-dose chest computed tomography for lung cancer screening in the United States. Methods Systematic literature searches were performed using 6 online databases and citation indexes for peer-reviewed studies, for articles published from 2013 to 2021. Studies were classified into 3 perspectives, based on the study’s unit of analysis: system, health-care provider, and patient. Barriers and facilitators identified for each study included in our final review were then coded and categorized using the Consolidate Framework for Implementation Research domains. Results At the system level, the 2 most common constructs were external policy and incentives and executing the implementation process. At the provider level, the most common constructs were evidence strength and quality of the intervention characteristics, patient needs and resources, implementation climate, and an individual’s knowledge and beliefs about the intervention. At the patient level, the most common constructs were patient needs and resources, individual’s knowledge and beliefs about the intervention, and engaging in the implementation process. These constructs can act as facilitators or barriers to lung cancer screening implementation. Conclusions Applying the Consolidate Framework for Implementation Research domains and constructs to understand and specify factors facilitating uptake of lung cancer screening as well as cataloging the lessons learned from previous efforts helps inform the development and implementation processes of lung cancer screening programs in the community setting. Registration PROSPERO, CRD42021247677.
Estimation of the Number of Individuals Living With Metastatic Cancer in the United States
Authors: Lisa Gallicchio, Theresa P Devasia, Emily Tonorezos, Michelle A Mollica, Angela Mariotto
Journal: JNCI Journal of the National Cancer Institute (2022)

The purpose of this study was to estimate the number of individuals living with metastatic breast, prostate, lung, colorectal, or bladder cancer or metastatic melanoma in the United States using population-based data.A back-calculation method was used to estimate the number of individuals living with metastatic cancer for each cancer type from US cancer mortality and survival statistics from the Surveillance, Epidemiology, and End Results registries. The percentages of those living with metastatic cancer who advanced to metastatic disease from early stage cancer vs who were diagnosed with metastatic cancer de novo were calculated. One- and 5-year relative survival rates for de novo metastatic cancer were compared by year of diagnosis to assess time trends in survival.It is estimated that, in 2018, 623 405 individuals were living with metastatic breast, prostate, lung, colorectal, or bladder cancer, or metastatic melanoma in the United States. This number is expected to increase to 693 452 in 2025. In 2018, the percentage of metastatic cancer survivors who were initially diagnosed with early stage cancer and advanced to metastatic cancer ranged from 30% for lung cancer to 72% for bladder cancer.This study demonstrates increasing numbers of individuals living with metastatic cancer of the 6 most common cancer types in the United States. This information is critical for informing the allocation of research efforts and healthcare infrastructure needed to address the needs of these individuals.
The WHO essential medicines list AWaRe book: from a list to a quality improvement system
Authors: Michael Sharland, Veronica Zanichelli, Loice Achieng Ombajo, Joel Bazira, Bernadette Cappello, Ronald Chitatanga, Pem Chuki, Sumanth Gandra, Haileyesus Getahun, Stephan Harbarth, Mark Loeb, Marc Mendelson, Lorenzo Moja, Celine Pulcini, Hatim Sati, Evelina Tacconelli, Mei Zeng, Benedikt Huttner
Journal: Clinical Microbiology and Infection (2022)
Visualization of Parkinsonian Tongue Tremor on Ultrasonography
Authors: Masakazu Hirose, Takamichi Kitagawa, Toshihiko Suenaga
Journal: JAMA Neurology (2022)

This case report describes involuntary trembling of the tongue accompanied by throat discomfort and affected voice quality in a patient with a history of hypertension and ventricular extrasystole.
Incubation Period of COVID-19 Caused by Unique SARS-CoV-2 Strains
Authors: Yu Wu, Liangyu Kang, Zirui Guo, Jue Liu, Min Liu, Wannian Liang
Journal: JAMA Network Open (2022)

Importance Several studies were conducted to estimate the average incubation period of COVID-19; however, the incubation period of COVID-19 caused by different SARS-CoV-2 variants is not well described. Objective To systematically assess the incubation period of COVID-19 and the incubation periods of COVID-19 caused by different SARS-CoV-2 variants in published studies. Data Sources PubMed, EMBASE, and ScienceDirect were searched between December 1, 2019, and February 10, 2022. Study Selection Original studies of the incubation period of COVID-19, defined as the time from infection to the onset of signs and symptoms. Data Extraction and Synthesis Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline, 3 reviewers independently extracted the data from the eligible studies in March 2022. The parameters, or sufficient information to facilitate calculation of those values, were derived from random-effects meta-analysis. Main Outcomes and Measures The mean estimate of the incubation period and different SARS-CoV-2 strains. Results A total of 142 studies with 8112 patients were included. The pooled incubation period was 6.57 days (95% CI, 6.26-6.88) and ranged from 1.80 to 18.87 days. The incubation period of COVID-19 caused by the Alpha, Beta, Delta, and Omicron variants were reported in 1 study (with 6374 patients), 1 study (10 patients), 6 studies (2368 patients) and 5 studies (829 patients), respectively. The mean incubation period of COVID-19 was 5.00 days (95% CI, 4.94-5.06 days) for cases caused by the Alpha variant, 4.50 days (95% CI, 1.83-7.17 days) for the Beta variant, 4.41 days (95% CI, 3.76-5.05 days) for the Delta variant, and 3.42 days (95% CI, 2.88-3.96 days) for the Omicron variant. The mean incubation was 7.43 days (95% CI, 5.75-9.11 days) among older patients (ie, aged over 60 years old), 8.82 days (95% CI, 8.19-9.45 days) among infected children (ages 18 years or younger), 6.99 days (95% CI, 6.07-7.92 days) among patients with nonsevere illness, and 6.69 days (95% CI, 4.53-8.85 days) among patients with severe illness. Conclusions and Relevance The findings of this study suggest that SARS-CoV-2 has evolved and mutated continuously throughout the COVID-19 pandemic, producing variants with different enhanced transmission and virulence. Identifying the incubation period of different variants is a key factor in determining the isolation period.
COVID-19 Disease Severity in Persons Infected With Omicron BA.1 and BA.2 Sublineages and Association With Vaccination Status
Authors: Adeel A. Butt, Soha R. Dargham, Peter Coyle, Hadi M. Yassine, Abdullatif Al-Khal, Abdul-Badi Abou-Samra, Laith J. Abu-Raddad
Journal: JAMA Internal Medicine (2022)

This retrospective study compares the severity of SARS-CoV-2 infection among persons infected with BA.1 and BA.2 sublineages by vaccination status.
Association of Chronic Disease With Patient Financial Outcomes Among Commercially Insured Adults
Authors: Nora V. Becker, John W. Scott, Michelle H. Moniz, Erin F. Carlton, John Z. Ayanian
Journal: JAMA Internal Medicine (2022)

The bidirectional association between health and financial stability is increasingly recognized.To describe the association between chronic disease burden and patients' adverse financial outcomes.This cross-sectional study analyzed insurance claims data from January 2019 to January 2021 linked to commercial credit data in January 2021 for adults 21 years and older enrolled in a commercial preferred provider organization in Michigan.Thirteen common chronic conditions (cancer, congestive heart failure, chronic kidney disease, dementia, depression and anxiety, diabetes, hypertension, ischemic heart disease, liver disease, chronic obstructive pulmonary disease and asthma, serious mental illness, stroke, and substance use disorders).Adjusted probability of having medical debt in collections, nonmedical debt in collections, any delinquent debt, a low credit score, or recent bankruptcy, adjusted for age group and sex. Secondary outcomes included the amount of medical, nonmedical, and total debt among individuals with nonzero debt.The study population included 2 854 481 adults (38.4% male, 43.3% female, 12.9% unknown sex, and 5.4% missing sex), 61.4% with no chronic conditions, 17.7% with 1 chronic condition, 14.8% with 2 to 3 chronic conditions, 5.4% with 4 to 6 chronic conditions, and 0.7% with 7 to 13 chronic conditions. Among the cohort, 9.6% had medical debt in collections, 8.3% had nonmedical debt in collections, 16.3% had delinquent debt, 19.3% had a low credit score, and 0.6% had recent bankruptcy. Among individuals with 0 vs 7 to 13 chronic conditions, the predicted probabilities of having any medical debt in collections (7.6% vs 32%), any nonmedical debt in collections (7.2% vs 24%), any delinquent debt (14% vs 43%), a low credit score (17% vs 47%) or recent bankruptcy (0.4% vs 1.7%) were all considerably higher for individuals with more chronic conditions and increased with each added chronic condition. Among individuals with medical debt in collections, the estimated amount increased with the number of chronic conditions ($784 for individuals with 0 conditions vs $1252 for individuals with 7-13 conditions) (all P < .001). In secondary analyses, results showed significant variation in the likelihood and amount of medical debt in collections across specific chronic conditions.This cross-sectional study of commercially insured adults linked to patient credit report outcomes shows an association between increasing burden of chronic disease and adverse financial outcomes.
Symptomatic Bradycardia
Authors: Mazen M. Kawji
Journal: JAMA Internal Medicine (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Five-Year Allograft Survival for Recipients of Kidney Transplants From Hepatitis C Virus Infected vs Uninfected Deceased Donors in the Direct-Acting Antiviral Therapy Era
Authors: Douglas E. Schaubel, Amelia H. Tran, Peter L. Abt, Vishnu S. Potluri, David S. Goldberg, Peter P. Reese
Journal: JAMA (2022)

This cohort study examines the validity of the Kidney Donor Profile Index’s hepatitis C virus (HCV) penalty during the direct-acting antiviral era by comparing 5-year allograft survival between recipients of kidneys from HCV-RNA–positive donors vs HCV-RNA–negative donors.
Incremental Value of Polygenic Risk Scores in Primary Prevention of Coronary Heart Disease
Authors: Jacob William Groenendyk, Philip Greenland, Sadiya S. Khan
Journal: JAMA Internal Medicine (2022)

Risk prediction for coronary heart disease (CHD) is a cornerstone of primary prevention strategies. Polygenic risk scores (PRSs) have emerged as a new approach to predict risk in asymptomatic people. Polygenic risk scores for CHD have been studied in several populations, but there is lack of agreement about the incremental value of PRS beyond traditional risk factor scores in the primary prevention of CHD.This narrative review critically appraised the 5 most highly cited studies published through 2021 that also included a large number (>45 000) of single-nucleotide variations (formerly single-nucleotide polymorphisms) and evaluated the incremental value of PRS in CHD risk prediction according to published PRS reporting standards. The cohorts studied included the Atherosclerosis Risk in Communities Study, FINRISK, the Framingham Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the UK Biobank. All of the studies focused predominantly on populations of European ancestry. The hazard ratio per standard deviation of PRS ranged from 1.24 (95% CI, 1.15-1.34) to 1.74 (95% CI, 1.61-1.86). The C statistic for PRS alone ranged from 0.549 to 0.623. The change in C statistic when PRS was added to a standard risk factor model ranged between -0.001 to +0.021. Net reclassification index was reported in 4 of the 5 studies and varied from 0.001 to 0.097. At a sensitivity (true-positive rate) of 90%, positive predictive values ranged from 1.8% to 16.6%, and false-positive rates ranged from 77.1% to 85.7%.In this review, PRS was significantly associated with CHD risk in all studies. The degree of improvement in C statistic and the net reclassification indexes when PRS was added to traditional risk scores ranged from negligible to modest. Based on established metrics to assess risk prediction scores, the addition of PRS to traditional risk scores does not appear to provide meaningful improvements in clinical decision-making in primary prevention populations.
Modeling Cost and Outcomes of SARS-CoV-2 School Testing Programs
Authors: Jennifer E. Schuster, Ibukunoluwa C. Kalu, Jennifer L. Goldman
Journal: JAMA Pediatrics (2022)

To the Editor We read with interest the article by Bilinski et al1 modeling transmission outcomes and cost of SARS-CoV-2 school testing programs. It is crucial to understand the realities of screening and surveillance in kindergarten through 12th-grade (K-12) testing programs when determining value.
Compassionate Use of Tecovirimat for the Treatment of Monkeypox Infection
Authors: Angel N. Desai, George R. Thompson, Sonja M. Neumeister, Anna M. Arutyunova, Katelyn Trigg, Stuart H. Cohen
Journal: JAMA (2022)

This case series describes the clinical resolution of systemic symptoms and lesions, along with any adverse events, in patients with monkeypox infection who were treated with tecovirimat on a compassionate use basis.
Cash Transfers and Reducing Child Poverty in the US
Authors: Benard P. Dreyer
Journal: JAMA Pediatrics (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Association of Fatal Overdose Notification Letters With Prescription of Benzodiazepines
Authors: Marcella A. Kelley, Roneet Lev, Jonathan Lucas, Tara Knight, Emily Stewart, Michael Menchine, Jason N. Doctor
Journal: JAMA Internal Medicine (2022)

This secondary analysis of a randomized clinical trial examines the association of receipt of an injunction letter from a medical examiner following a patient’s drug overdose with patterns of benzodiazepine prescribing among physicians.